tbuckley/cabot-search huggingface dataset:
Human Papillomavirus Vaccine Impact and Effectiveness Through 12 Years After Vaccine Introduction in the United States, 2003 to 2018
Authors: Hannah G. Rosenblum, Rayleen M. Lewis, Julia W. Gargano, Troy D. Querec, Elizabeth R. Unger, Lauri E. Markowitz
Journal: Annals of Internal Medicine (2022)

Background: Human papillomavirus (HPV) vaccination was introduced in 2006 for females and in 2011 for males. Objective: To estimate vaccine impact and effectiveness against quadrivalent HPV vaccine (4vHPV)–type prevalent infection among sexually experienced U.S. females and vaccine effectiveness for sexually experienced U.S. males. Design: NHANES (National Health and Nutrition Examination Survey) conducted in 2003 to 2006 (prevaccine era) and in 2007 to 2010, 2011 to 2014, and 2015 to 2018 (vaccine eras). Setting: Nationally representative U.S. surveys. Participants: Sexually experienced participants aged 14 to 24 years. Intervention: U.S. HPV vaccination program. Measurements: Participant-collected cervicovaginal and penile specimens were tested for HPV DNA. The prevalences of 4vHPV and non-4vHPV types were estimated in each era for females and in 2013 to 2016 for males. Prevalences among the female population overall, vaccinated females, and unvaccinated females were compared in vaccine eras versus the prevaccine era (vaccine impact). Within each vaccine era, prevalence among vaccinated females was compared with that among unvaccinated females (vaccine effectiveness). Vaccine impact and effectiveness were estimated as (1 − prevalence ratio) · 100. Results: Among sexually experienced females aged 14 to 24 years, the impact on 4vHPV-type prevalence in 2015 to 2018 was 85% overall, 90% among vaccinated females, and 74% among unvaccinated females. No significant declines were found in non–4vHPV-type prevalence. Vaccine effectiveness ranged from 60% to 84% during vaccine eras for females and was 51% during 2013 to 2016 for males. Limitation: Self- or parent-reported vaccination history and small numbers in certain subgroups limited precision. Conclusion: Nationally representative data show increasing impact of the vaccination program and herd protection. Vaccine effectiveness estimates will be increasingly affected by herd effects. Primary Funding Source: Centers for Disease Control and Prevention.
Preoperative and perioperative risk factors, and risk score development for prosthetic joint infection due to Staphylococcus aureus: a multinational matched case-control study
Authors: Reinaldo Espindola, Venanzio Vella, Natividad Benito, Isabel Mur, Sara Tedeschi, Nicolò Rossi, Johannes G.E. Hendriks, Luisa Sorlí, Oscar Murillo, Mathew Scarborough, Claire Scarborough, Jan Kluytmans, Mateo Carlo Ferrari, Mathias W. Pletz, Iain Mcnamara, Rosa Escudero-Sanchez, Cedric Arvieux, Cecile Batailler, Frédéric-Antoine Dauchy, Wai-Yan Liu, Jaime Lora-Tamayo, Julia Praena, Andrew Ustianowski, Elisa Cinconze, Michele Pellegrini, Fabio Bagnoli, Jesús Rodríguez-Baño, Maria Dolores Del Toro, Nienke Cuperus, Giuseppe Manfré, Eleonora Zamparini, Stéphanie Verhagen, Juan P. Horcajada, Joan Gómez Junyent, Albert Alier, Laura Soldevila, Miranda van Rijen, Jannie Romme, Juliane Ankert, Celia Whitehouse, Adrian Jones, Javier Cobo, Javier Moreno, Anne Meheut, Claire Gledel, Pauline Perreau, Remco J.A. van Wensen, Gabriella Lindergard
Journal: Clinical Microbiology and Infection (2022)
Benefit of Extended Surveillance of Low-Risk Pancreatic Cysts After 5-Year Stability: A Systematic Review and Meta-Analysis
Authors: Ankit Chhoda, Sidhant Singh, Amar H. Sheth, Alyssa A. Grimshaw, Craig G. Gunderson, Prabin Sharma, John W. Kunstman, Anup Sharma, Nita Ahuja, Tamas A. Gonda, James J. Farrell
Journal: Clinical Gastroenterology and Hepatology (2022)
Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy
Authors: Gabrielle Norrish, Aoife Cleary, Ella Field, Elena Cervi, Olga Boleti, Lidia Ziółkowska, Iacopo Olivotto, Diala Khraiche, Giuseppe Limongelli, Aris Anastasakis, Robert Weintraub, Elena Biagini, Luca Ragni, Terence Prendiville, Sophie Duignan, Karen McLeod, Maria Ilina, Adrian Fernandez, Chiara Marrone, Regina Bökenkamp, Anwar Baban, Peter Kubus, Piers E.F. Daubeney, Georgia Sarquella-Brugada, Sergi Cesar, Sabine Klaassen, Tiina H. Ojala, Vinay Bhole, Constancio Medrano, Orhan Uzun, Elspeth Brown, Ferran Gran, Gianfranco Sinagra, Francisco J. Castro, Graham Stuart, Hirokuni Yamazawa, Roberto Barriales-Villa, Luis Garcia-Guereta, Satish Adwani, Katie Linter, Tara Bharucha, Esther Gonzales-Lopez, Ana Siles, Torsten B. Rasmussen, Margherita Calcagnino, Caroline B. Jones, Hans De Wilde, Toru Kubo, Tiziana Felice, Anca Popoiu, Jens Mogensen, Sujeev Mathur, Fernando Centeno, Zdenka Reinhardt, Sylvie Schouvey, Perry M. Elliott, Juan Pablo Kaski
Journal: Journal of the American College of Cardiology (2022)

Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.
Abstract A008: <i>TP53</i> field defects in uterine fluid are associated with ovarian cancer risk
Authors: Rosana Risques, Thomas H. Smith, Zachary K. Norgaard, Roniz Katz, Fang Yin Lo, Elizabeth K. Schmidt, Jacob E. Higgins, Martin Filipits, Intidhar Labidi-Galy, David Cibula, Lukáš Dostálek, Gabriel Jelenek, Magdalena Plch, Jiří Bouda, Alexander Mustea, Mateja Condic, Sabine Grill, Noreen Gleeson, Peter Oppelt, Gunda Pristauz-Telsnigg, Adriaan Vanderstichele, Siel Obrecht, Adam Rosenthal, Paul Speiser, Jesse Salk
Journal: Cancer Research (2022)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR005) of the Conference Proceedings. Citation Format: Rosana Risques, Thomas H. Smith, Zachary K. Norgaard, Roniz Katz, Fang Yin Lo, Elizabeth K. Schmidt, Jacob E. Higgins, Martin Filipits, Intidhar Labidi-Galy, David Cibula, Lukáš Dostálek, Gabriel Jelenek, Magdalena Plch, Jiří Bouda, Alexander Mustea, Mateja Condic, Sabine Grill, Noreen Gleeson, Peter Oppelt, Gunda Pristauz-Telsnigg, Adriaan Vanderstichele, Siel Obrecht, Adam Rosenthal, Paul Speiser, Jesse Salk. TP53 field defects in uterine fluid are associated with ovarian cancer risk [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A008.
Airway remodelling rather than cellular infiltration characterizes both type2 cytokine biomarker‐high and ‐low severe asthma
Authors: Latifa Khalfaoui, Fiona A. Symon, Simon Couillard, Beverley Hargadon, Rekha Chaudhuri, Steve Bicknell, Adel H. Mansur, Rahul Shrimanker, Timothy S. C. Hinks, Ian D. Pavord, Stephen J. Fowler, Vanessa Brown, Lorcan P. McGarvey, Liam G. Heaney, Cary D. Austin, Peter H. Howarth, Joseph R. Arron, David F. Choy, Peter Bradding
Journal: Allergy (2022)

Abstract Background The most recognizable phenotype of severe asthma comprises people who are blood eosinophil and FeNO‐high, driven by type 2 (T2) cytokine biology, which responds to targeted biological therapies. However, in many people with severe asthma, these T2 biomarkers are suppressed but poorly controlled asthma persists. The mechanisms driving asthma in the absence of T2 biology are poorly understood. Objectives To explore airway pathology in T2 biomarker‐high and ‐low severe asthma. Methods T2 biomarker‐high severe asthma (T2‐high, n = 17) was compared with biomarker‐intermediate (T2‐intermediate, n = 21) and biomarker‐low (T2‐low, n = 20) severe asthma and healthy controls ( n = 28). Bronchoscopy samples were processed for immunohistochemistry, and sputum for cytokines, PGD 2 and LTE 4 measurements. Results Tissue eosinophil, neutrophil and mast cell counts were similar across severe asthma phenotypes and not increased when compared to healthy controls. In contrast, the remodelling features of airway smooth muscle mass and MUC5AC expression were increased in all asthma groups compared with health, but similar across asthma subgroups. Submucosal glands were increased in T2‐intermediate and T2‐low asthma. In spite of similar tissue cellular inflammation, sputum IL‐4, IL‐5 and CCL26 were increased in T2‐high versus T2‐low asthma, and several further T2‐associated cytokines, PGD 2 and LTE 4 , were increased in T2‐high and T2‐intermediate asthma compared with healthy controls. Conclusions Eosinophilic tissue inflammation within proximal airways is suppressed in T2 biomarker‐high and T2‐low severe asthma, but inflammatory and structural cell activation is present, with sputum T2‐associated cytokines highest in T2 biomarker‐high patients. Airway remodelling persists and may be important for residual disease expression beyond eosinophilic exacerbations. Registered at ClincialTrials.gov : NCT02883530.
Rare and Common Genetic Variation Underlying the Risk of Hypertrophic Cardiomyopathy in a National Biobank
Authors: Kiran J. Biddinger, Sean J. Jurgens, Dimitri Maamari, Liam Gaziano, Seung Hoan Choi, Valerie N. Morrill, Jennifer L. Halford, Amit V. Khera, Steven A. Lubitz, Patrick T. Ellinor, Krishna G. Aragam
Journal: JAMA Cardiology (2022)

Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death in young people. Although rare genetic variants are well-established contributors to HCM risk, common genetic variants have recently been implicated in disease pathogenesis.To assess the contributions of rare and common genetic variation to risk of HCM in the general population.This cohort study of the UK Biobank (data from 2006-2010) and the Mass General Brigham Biobank (2010-2019) assessed the relative and joint contributions of rare genetic variants and a common variant (polygenic) score to risk of HCM. Both rare and common variant predictors were then evaluated in the context of relevant clinical risk factors. Data analysis was conducted from May 2021 to February 2022.Pathogenic rare variants, common-variant (polygenic) score, and clinical risk factors.Risk of HCM.The primary study population comprised 184 511 individuals from the UK Biobank. Mean (SD) age was 56 (8) years, 83 690 (45%) of participants were men, and 204 (0.1%) participants had HCM. Of 51 genes included in clinical genetic testing panels for HCM, pathogenic or likely pathogenic variants in 14 core genes (designated by the American College of Medical Genetics and Genomics [ACMG]) were associated with 55-fold higher odds (95% CI, 35-83) of HCM, while those in the remaining 37 non-ACMG genes were not significantly associated with HCM (OR, 1.8; 95% CI, 0.6-4.0). ClinVar pathogenic or likely pathogenic mutations in MYBPC3 (OR, 72; 95% CI, 39-124) and MYH7 (OR, 61; 95% CI, 26-121) were strongly associated with HCM, as were loss-of-function variants in ALPK3 (OR, 13; 95% CI, 4.4-28). A polygenic score was strongly associated with HCM (OR per SD increase in score, 1.6; 95% CI, 1.4-1.8), with concordant results in the Mass General Brigham Biobank. Genetic factors enhanced clinical risk prediction for HCM: addition of rare variant carrier status and the polygenic score to clinical risk factors (obesity, hypertension, atrial fibrillation, and coronary artery disease) improved the area under the receiver operator characteristic curve from 0.71 (95% CI, 0.65-0.77) to 0.82 (95% CI, 0.77-0.87).Both rare and common genetic variants contribute substantially to HCM susceptibility in the general population and improve HCM risk prediction beyond that achieved with clinical factors.
Treatment With Oral Propranolol for Refractory Classic Cutaneous Kaposi Sarcoma
Authors: Rafael Salido-Vallejo, Alberto González-Menchen, Carmen Alcántara-Reifs, Agustín España
Journal: JAMA Dermatology (2022)

This case report describes a Mediterranean HIV-negative man in his 60s with hypertension, osteoporosis, a history of flaccid paralysis after polio syndrome, and a 4-year history of progressive development of purplish, reddish cutaneous plaques and nodules limited to the lower limbs.
The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial
Authors: Alan Pollack, Theodore G Karrison, Alexander G Balogh, Leonard G Gomella, Daniel A Low, Deborah W Bruner, Jeffrey S Wefel, Andre-Guy Martin, Jeff M Michalski, Steve J Angyalfi, Himanshu Lukka, Sergio L Faria, George B Rodrigues, Marie-Claude Beauchemin, R Jeffrey Lee, Samantha A Seaward, Aaron M Allen, Drew C Monitto, Wendy Seiferheld, Oliver Sartor, Felix Feng, Howard M Sandler
Journal: The Lancet (2022)
Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults
Authors: Anurag Singh, Davide D’Amico, Pénélope A. Andreux, Andréane M. Fouassier, William Blanco-Bose, Mal Evans, Patrick Aebischer, Johan Auwerx, Chris Rinsch
Journal: Cell Reports Medicine (2022)

Targeting mitophagy to activate the recycling of faulty mitochondria during aging is a strategy to mitigate muscle decline. We present results from a randomized, placebo-controlled trial in middle-aged adults where we administer a postbiotic compound Urolithin A (Mitopure), a known mitophagy activator, at two doses for 4 months (NCT03464500). The data show significant improvements in muscle strength (∼12%) with intake of Urolithin A. We observe clinically meaningful improvements with Urolithin A on aerobic endurance (peak oxygen oxygen consumption [VO2]) and physical performance (6 min walk test) but do not notice a significant improvement on peak power output (primary endpoint). Levels of plasma acylcarnitines and C-reactive proteins are significantly lower with Urolithin A, indicating higher mitochondrial efficiency and reduced inflammation. We also examine expression of proteins linked to mitophagy and mitochondrial metabolism in skeletal muscle and find a significant increase with Urolithin A administration. This study highlights the benefit of Urolithin A to improve muscle performance.
Benefit of Biennial Fecal Occult Blood Screening on Colorectal Cancer in England: A Population-Based Case-Control Study
Authors: Alejandra Castanon, Dharmishta Parmar, Nathalie J Massat, Peter Sasieni, Stephen W Duffy
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background The English national bowel cancer screening program offering a guaiac fecal occult blood test began in July 2006. In randomized controlled trials of guaiac fecal occult blood test screening, reductions in mortality were accompanied by reductions in advanced stage colorectal cancer (CRC). We aimed to evaluate the effect of participation in the national bowel cancer screening program on stage-specific CRC incidence as a likely precursor of a mortality effect. Methods In this population-based case-control study, cases were individuals diagnosed with CRC aged 60-79 years between January 1, 2012, and December 31, 2013. Two controls per case were matched on geographic region, gender, date of birth, and year of first screening invitation. Screening histories were extracted from the screening database. Conditional logistic regression with correction for self-selection bias was used to estimate odds ratios (odds ratios corrected for self-selection bias [cOR]) and 95% confidence intervals (CIs) by Duke stage, sex, and age. Results 14 636 individuals with CRC and 29 036 without were eligible for analysis. The odds of CRC (any stage) were increased within 30 days of a screening test and decreased thereafter. No reduction in CRC (any stage) among screened individuals compared with those not screened was observed (cOR = 1.00, 95% CI = 0.89 to 1.15). However, screened individuals had lower odds of Duke stage D CRC (cOR = 0.68, 95% CI = 0.50 to 0.93). We estimate 435 fewer Duke D CRC by age 80 years in 100 000 people screened biennially between ages 60 and 74 years compared with an unscreened cohort. Conclusion The impact of colorectal screening on advanced CRC incidence suggests that the program will meet its aim of reducing mortality.
Covid-19: North Korean leader blames his party’s incompetence after 393 000 cases of fever reported in a day
Authors: Owen Dyer
Journal: BMJ (2022)

Covid-19: North Korean leader blames his party's incompetence after 393 000 cases of fever reported in a day Owen DyerNorth Korea's dictator Kim Jong-un has blamed the institutions of his own ruling Workers' Party for "incompetence and a lack of responsibility" in tackling a covid-19 outbreak that he characterised as "the biggest upheaval since the nation's founding."Only three days after the country acknowledged its first case, it reported 393 920 new "fever" cases in a 24 hour period ending on 15 May, indicating that more than 1.5% of the population had developed symptomatic disease in a single day.North Korea reported 18 000 new cases of fever over the previous 24 hours on 13 May, and 178 120 on 14 May.So far, 50 deaths have been reported.
Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia
Authors: Mariana L. Oliveira, Alexandra Veloso, Elaine G. Garcia, Sowmya Iyer, Clara Pereira, Vasco M. Barreto, David M. Langenau, João T. Barata
Journal: Leukemia (2022)

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric cancer. Amongst the wide array of driver mutations, 10% of T-ALL patients display gain-of-function mutations in the IL-7 receptor α chain (IL-7Rα, encoded by IL7R), which occur in different molecular subtypes of this disease. However, it is still unclear whether IL-7R mutational activation is sufficient to transform T-cell precursors. Also, which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here, we demonstrate that mutant IL7R alone is capable of inducing T-ALL with long-latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally, we find that mutant IL7R collaborates with Myc to induce early onset T-ALL in transgenic zebrafish, supporting a model where these pathways collaborate to drive leukemogenesis. T-ALLs co-expressing mutant IL7R and Myc activate STAT5 and AKT pathways, harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T-ALLs expressing Myc alone. Moreover, limiting-dilution cell transplantation experiments reveal that activated IL-7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T-ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.
Liver Colonization by Colorectal Cancer Metastases Requires YAP-Controlled Plasticity at the Micrometastatic Stage
Authors: Maria C. Heinz, Niek A. Peters, Koen C. Oost, Rik G.H. Lindeboom, Lisa van Voorthuijsen, Arianna Fumagalli, Mirjam C. van der Net, Gustavo de Medeiros, Joris H. Hageman, Ingrid Verlaan-Klink, Inne H.M. Borel Rinkes, Prisca Liberali, Martijn Gloerich, Jacco van Rheenen, Michiel Vermeulen, Onno Kranenburg, Hugo J.G. Snippert
Journal: Cancer Research (2022)

Abstract Micrometastases of colorectal cancer can remain dormant for years prior to the formation of actively growing, clinically detectable lesions (i.e., colonization). A better understanding of this step in the metastatic cascade could help improve metastasis prevention and treatment. Here we analyzed liver specimens of patients with colorectal cancer and monitored real-time metastasis formation in mouse livers using intravital microscopy to reveal that micrometastatic lesions are devoid of cancer stem cells (CSC). However, lesions that grow into overt metastases demonstrated appearance of de novo CSCs through cellular plasticity at a multicellular stage. Clonal outgrowth of patient-derived colorectal cancer organoids phenocopied the cellular and transcriptomic changes observed during in vivo metastasis formation. First, formation of mature CSCs occurred at a multicellular stage and promoted growth. Conversely, failure of immature CSCs to generate more differentiated cells arrested growth, implying that cellular heterogeneity is required for continuous growth. Second, early-stage YAP activity was required for the survival of organoid-forming cells. However, subsequent attenuation of early-stage YAP activity was essential to allow for the formation of cell type heterogeneity, while persistent YAP signaling locked micro-organoids in a cellularly homogenous and growth-stalled state. Analysis of metastasis formation in mouse livers using single-cell RNA sequencing confirmed the transient presence of early-stage YAP activity, followed by emergence of CSC and non-CSC phenotypes, irrespective of the initial phenotype of the metastatic cell of origin. Thus, establishment of cellular heterogeneity after an initial YAP-controlled outgrowth phase marks the transition to continuously growing macrometastases. Significance: Characterization of the cell type dynamics, composition, and transcriptome of early colorectal cancer liver metastases reveals that failure to establish cellular heterogeneity through YAP-controlled epithelial self-organization prohibits the outgrowth of micrometastases. See related commentary by LeBleu, p. 1870